The goal of this training grant proposal is to prepare predoctoral trainees for productive research careers in the field of signaling and cellular regulation. The training faculty consists of an outstanding, internationally recognized group of investigators in the Depts. of Chemistry and Biochemistry; Molecular, Cellular, Developmental Biology; Chemical and Biological Engineering; and Physics, who study basic cell regulatory mechanisms through discovery and characterization of key components in signaling pathways, transfer of biological information through protein conformational changes and posttranslational modifications, computational analysis and mathematical modeling of complex biological pathways, and formulation of new therapeutic strategies for human diseases. The program provides students with rigorous training in experimental design, scientific technique, and data evaluation, exposure to a wide range of scientific disciplines, training in classroom teaching, opportunities for scientific presentation, and training in standards for professional conduct. In Year 1, students take coursework and teaching duties in their home departments, and carry out laboratory rotations. At the end of Year 1, students choose a thesis advisor and elect to join this training program. In Year 2, students begin research and take elective coursework tailored to this program. Written and oral qualifying exams including the defense of a dissertation research proposal are required to advance to Ph.D. candidacy. In Years 3 and beyond, students obtain high caliber research training through the thesis project, with progress monitored yearly until graduation. Students add to their breadth and knowledge by participating in program symposia, supergroups, journal clubs, and seminars, and by presenting their work before large audiences. Students complete the program by defending a doctoral dissertation and receive a Ph.D. degree in Biochemistry or MCDB. Most students finish within 6 years of matriculation, and go on to postdoctoral training and careers in academia, research institutes, or pharmaceutical/biotechnology companies.